Related Experiment Video

Updated: Jun 1, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
06:21

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Genetic variations in multiple drug action pathways and survival in advanced stage non-small cell lung cancer treated

Yafei Li1, Zhifu Sun, Julie M Cunningham

  • 1Department of Health Sciences Research, Rochester, Minnesota, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 4, 2011
PubMed
Abstract

Insights

Genetic variations in epidermal growth factor receptor (EGFR) and glutathione pathways impact survival for advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy. These findings may guide personalized treatment strategies for lung cancer.

Area of Science:

  • Oncology
  • Pharmacogenomics
  • Molecular Biology

Background:

  • Genetic variations can influence individual responses to anticancer drugs.
  • Understanding these variations is crucial for optimizing lung cancer treatment and prognosis.
  • Key biological pathways implicated include glutathione metabolism, DNA repair, cell cycle, and EGFR signaling.

Purpose of the Study:

  • To investigate the association between genetic variants in four biological pathways and survival outcomes.
  • To analyze the impact of these genetic variants in patients with advanced stage non-small cell lung cancer (NSCLC) receiving chemotherapy.

Main Methods:

  • Genotyping of 894 tagging single-nucleotide polymorphisms (SNPs) in 70 genes across the four pathways.
  • Analysis of overall survival in a cohort of 1,076 patients.
  • Association analysis performed at both SNP and whole-gene levels, stratified by chemotherapy regimens.

Main Results:

  • Genetic variations in GSS (glutathione) and MAP3K1 (EGFR) were associated with poorer overall survival.
  • In platinum plus taxane treatment, MAP3K1 variants showed a hazardous effect, while RAF1 variants had a protective effect.
  • In platinum plus gemcitabine treatment, RAF1 and GPX5 variants were protective, whereas NRAS and GPX7 variants were hazardous.

Conclusions:

  • Common genetic variations in EGFR and glutathione pathways are associated with overall survival in advanced NSCLC patients.
  • These findings highlight the potential of pharmacogenomics in tailoring chemotherapy regimens (platinum, taxane, gemcitabine) for improved lung cancer outcomes.

More Related Videos

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer07:59

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...